2,500 living donor kidney transplants: a single-center experience

OBJECTIVE: To review a single center's experience and outcome with living donor transplants. SUMMARY BACKGROUND DATA: Outcome after living donor transplants is better than after cadaver donor transplants. Since the inception of the authors' program, they have performed 2,540 living donor transplants. For the most recent cohort of recipients, improvements in patient care and immunosuppressive protocols have improved outcome. In this review, the authors analyzed outcome in relation to protocol. METHODS: The authors studied patient and graft survival by decade. For those transplanted in the 1990s, the impact of immunosuppressive protocol, donor source, diabetes, and preemptive transplantation was analyzed. The incidence of rejection, posttransplant steroid-related complications, and return to work was determined. Finally, multivariate analysis was used to study risk factors for worse 1-year graft survival and, for those with graft function at 1 year, to study risk factors for worse long-term survival. RESULTS: For each decade since 1960, outcome has improved after living donor transplants. Compared with patients transplanted in the 1960s, those transplanted in the 1990s have better 8-year actuarial patient and graft survival rates. Death with function and chronic rejection have continued to be a major cause of graft loss, whereas acute rejection has become a rare cause of graft loss. Cardiovascular deaths have become a more predominant cause of patient death; infection has decreased. Donor source (e.g., ideally HLA-identical sibling) continues to be important. For living donor transplants, rejection and graft survival rates are related to donor source. The authors show that patients who had preemptive transplants or less than 1 year of dialysis have better 5-year graft survival and more frequently return to full-time employment. Readmission and complications remain problems; of patients transplanted in the 1990s, only 36% never required readmission. Similarly, steroid-related complications remain common. The authors' multivariate analysis shows that the major risk factor for worse 1-year graft survival was delayed graft function. For recipients with 1-year graft survival, risk factors for worse long-term outcome were pretransplant smoking, pretransplant peripheral vascular disease, pretransplant dialysis for more than 1 year, one or more acute rejection episodes, and donor age older than 55. CONCLUSIONS: These data show that the outcome of living donor transplants has continued to improve. However, for living donors, donor source affects outcome. The authors also identify other major risk factors affecting both short- and long-term outcome.     

Causes of kidney allograft loss in a large pediatric population at a single center

At our institution, 521 kidney transplants were performed in 429 children (mean age 8.7±5.6-years) between 1969 and 1991. Of these transplants, 408 were primary, 113 were retransplants, 347 were living related, 171 were cadaver, and 3 were living nonrelated. Immunosuppression consisted of prednisone, azathioprine, and Minnesota antilymphocyte globulin (non-CSA) in 339 patients, total lymphoid irradiation in 8, and, more recently, cyclosporine (CSA) in addition in 168 patients. Average followup was 8.8±6.0 years.Actuarial graft survival in the non-CSA versus CSA groups at 1 year was 77.0% versus 85.7%; at 5 years, 59.6% versus 71.9%. Of 136 non-CSA patients, causes of graft loss at 5 years included: chronic rejection in 55 (40.4%), acute rejection in 27 (19.9%), recurrent disease in 16 (11.8%), technical complications in 8 (5.9%), infectious complications in 4 (2.9%), other causes in 5 (3.7%), and death with a functioning graft in 21 (15.4%). Of 40 CSA patients, causes of graft loss at 5 years included: chronic rejection in 16 (40.0%), acute rejection in 8 (20.0%), recurrent disease in 6 (15.0%), technical complications in 3 (7.5%), other causes in 2 (5.0%), and death with a functioning graft in 5 (12.5%).The causes of graft loss did not significantly differ in the non-CSA and CSA groups. Chronic rejection was the most common cause of graft loss in both groups. Research focusing on chronic rejection is needed to improve graft outcome in pediatric kidney transplantation.     

What happens to the kidney in an SPK transplant when the pancreas fails due to a technical complication?

Abstract:  We examined a group of SPK recipients that had early (<90 d post-transplant) pancreas graft failure caused by a technical complication, and looked at outcomes of the kidney graft in these recipients. Of 289 SPK transplants, 36 (12.5%) had early pancreas graft failure because of a technical complication: thrombosis (n = 16), leak (n = 5), infection (n = 14), and pancreatitis (n = 1). Once the pancreas was lost, there was a high incidence of subsequent kidney graft failure. Kidney graft survival in these 36 recipients was 71.4% at one yr and 59.5% at three yr, significantly inferior compared to recipients that did not have early failure of the pancreas (86% at one yr and 82% at three yr, p < 0.001). Of the 36 recipients with early pancreas loss, 18 have gone on to failure of the kidney graft. Causes included thrombosis (n = 3), infection (n = 1), death with function (n = 6), chronic rejection (n = 4), ischemia (n = 1), and other (n = 3). Of the 18 kidney graft failures, nine occurred within three months after loss of the pancreas graft, usually either because of graft thrombosis, or patient death (usually from systemic sepsis). Multivariate analysis showed technical failure of the pancreas to be the most significant risk factor for kidney graft loss (HR = 2.08, p = 0.006).     

Effect of donor/recipient body weight mismatch on patient and graft outcome in living-donor kidney transplantation

BACKGROUND/AIMS: There have been conflicting reports showing that kidneys from small donors may be at risk for graft loss if they are transplanted into large recipients. The aim of this work was to examine the donor/recipient body weight ratio (D/RBWR) on patient and graft outcome. METHODS: During the period from January 1990 to January 2002, 856 kidney transplants were performed. Of these, 776 kidney transplant recipients were selected after exclusion of pediatric, second transplant patients and those with a body mass index of 35. All patients achieved a minimum follow-up of 1-year. According to D/RBWR, patients were divided into 3 groups: low (0.9), medium (0.91-1.2) and high (1.2). Data were collected on graft function, acute and chronic rejection, post-transplant complications, and 1- and 5-year graft and patient survival. RESULTS: There was a statistically significant increase in the incidence of chronic rejection, post-transplant hypertension and diabetes mellitus in the low group. The incidence and frequency of acute rejection episodes were nearly the same in the 3 groups. Graft function, estimated by serum creatinine at 1 year, was significantly lower in the low group. The 5-year graft and patient survival was 71, 80, 88 and 81, 85 and 92%, in the low, medium and high groups, respectively. CONCLUSIONS: We conclude that a low D/RBWR may contribute to inferior long-term renal allograft survival. The hyperfiltration hypothesis due to low nephron mass in the low D/RBWR group may explain these findings.     

Kidney transplantation from donation after cardiac death donors: lack of impact of delayed graft function on post‐transplant outcomes

Singh RP, Farney AC, Rogers J, Zuckerman J, Reeves‐Daniel A, Hartmann E, Iskandar S, Adams P, Stratta RJ. Kidney transplantation from donation after cardiac death donors: lack of impact of delayed graft function on post‐transplant outcomes.
Clin Transplant 2011: 25: 255–264. © 2010 John Wiley & Sons A/S. Abstract: Introduction: Delayed graft function (DGF) is more common in recipients of kidney transplants from donation after cardiac death (DCD) donors compared to donation after brain death (DBD) donors. Methods: Single‐center retrospective study to evaluate the impact of DGF on controlled (Maastricht category III) DCD donor kidney transplant outcomes. Results: From 10/01 to 6/08, 578 adult deceased donor kidney transplants were performed including 70 (12%) from DCD and 508 (88%) from DBD donors. Mean follow‐up was 36 months. DCD donor kidney transplants had significantly greater rates of DGF (57% DCD vs. 21% DBD, p < 0.0001)) and acute rejection (29% DCD vs. 16% DBD, p = 0.018) compared to DBD donor kidney transplants, but patient and graft survival rates were similar. DBD donor kidney transplants with DGF (n = 109) had significantly greater rates of death‐censored graft loss (12.5% DCD vs. 31% DBD), primary non‐function (0 DCD vs. 10% DBD) and higher 2 year mean serum creatinine levels (1.4 DCD vs. 2.7 mg/dL DBD) compared to DCD donor kidney transplants with DGF (n = 40, all p < 0.04). On univariate analysis, the presence of acute rejection and older donor age were the only significant risk factors for death‐censored graft loss in DCD donor kidney transplants, whereas DGF was not a risk factor. Conclusion: Despite higher rates of DGF and acute rejection in DCD donor kidney transplants, subsequent outcomes in DCD donor kidney transplants with DGF are better than in DBD donor kidney transplants experiencing DGF, and similar to outcomes in DCD donor kidney transplants without DGF.     

Causes of renal allograft loss. Progress in the 1980s, challenges for the 1990s.

A variety of refinements in the care of kidney transplant recipients have been instituted over the past decade. The authors studied the overall impact of these refinements on kidney allograft losses at a single institution. To do this they compared the causes and rates of graft loss for primary kidney transplants in the 1970s (January 1, 1970 to December 31, 1979; n = 1012; 657 nondiabetics, 355 diabetics; 617 living donors, 395 cadaver donors) versus the 1980s (January 1, 1980 to December 31, 1989; n = 1,384; 756 nondiabetics, 628 diabetics; 740 living donors, 644 cadaver donors). Overall patient survival improved significantly, with rates at 1, 5, and 10 years of 94%, 84%, and 68% for the 1980s, compared with 86%, 69%, and 57% for the 1970s (p less than 0.001). Actuarial graft survival also improved significantly, with rates at 1, 5, and 10 years of 86%, 71%, and 52% for the 1980s, compared with 73%, 58%, and 43% for the 1970s (p less than 0.001). This improvement occurred even though there were proportionately more cadaver donors and diabetic recipients in the 1980s. For both decades combined, 24% of the lost grafts were due to chronic rejection, 18% to cardiovascular causes of death with function, 13% to infectious causes of death with function, and 11% to acute rejection. The overall gain in graft survival rates in the 1980s was principally due to fewer cases of acute rejection and fewer infectious deaths. Improvement in graft survival due to the two leading causes--chronic rejection and cardiovascular causes of death--was relatively small, if any. These data indicate that future kidney transplantation research should emphasize prevention of chronic rejection and cardiovascular death.     

Increasing the donor pool using en bloc pediatric kidneys for transplant

OBJECTIVES: En bloc pediatric kidney transplants (EBPKT) are still a subject of controversy. The aim of this study was to determine whether acceptable long-term graft survival and function can be achieved in EBPKT compared with the transplant of single, cadaveric, adult donor kidneys. METHODS: A retrospective review was conducted of 66 recipients of en bloc kidneys from cadaveric pediatric donors and 434 patients who underwent transplantation with a single kidney from an adult donor between January 1990 and May 2002 at the authors' hospital. The recipients were well-matched demographically. Both transplant groups were analyzed for short- and long-term performance in terms of transplant outcome and quality of graft function. RESULTS: Overall death-censored actuarial graft survival rates at 1 and 5 years were 89.2% and 84.6% in the adult kidney transplants (AKT) and 83.3% and 81.1% in EBPKT, respectively (P=0.56). In the EBPKT group, graft function was improved over that observed in AKT. Vascular thrombosis was the most common cause of graft loss in EBPKT. Acute rejection occurred more frequently in AKT and Cox's regression analysis indicated that undergoing an AKT was a predictive factor for acute vascular rejection (adjusted risk ratio, 3.8; 95% confidence interval, 1.4-10.2; P=0.001). CONCLUSIONS: Overall graft survival was similar in both groups, vascular complications were the main cause of graft loss in EBPKT, and the EBPKT showed excellent long-term graft function and a low incidence of acute rejection.     

Similar risk profiles for post-transplant renal dysfunction and long-term graft failure: UNOS/OPTN database analysis

BACKGROUND: Renal dysfunction measured by serum creatinine (>1.5 mg/dL) at 1 year post-transplant correlates with long-term kidney graft survival. The purpose of this study was to compare the risk factors for elevated serum creatinine (SCr) >1.5 mg/dL at 1 year post-transplantation, and for long-term graft failure. METHODS: Between 1988 and 1999, 117,501 adult kidney transplants were reported to Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS). Of these, 96,091 were functioning at 1 year and SCr was available on 85,135 transplants. Donor and recipient demographics (age, sex, and race), transplant [living vs. cadaveric, previous transplantation, panel reactive antibody (PRA), human leukoocyte antigen (HLA) mismatch, cold ischemic time (CIT) and post-transplant delayed graft function (DGF), use of azathioprone vs. mycophenolate mofetil (MMF), cyclosporine A (CsA) vs. tacrolimus (Tac)], induction antibody, acute rejection within 1 year variables were used in the logistic regression model to estimate odds ratio (OR) for elevated 1 year serum creatinine (SCr). A Cox proportional hazard model was used to estimate the relative risk (RR) for long-term kidney graft failure with and without censoring for death with a functioning graft. RESULTS: Five-year actuarial graft survival for living donor transplant with SCr >1.5 and 1.5 mg/dL) declined from 54.5% in 1988 to 42.3% in 1999. There was a strong concordance between the key variables, such as cadaveric transplant, increasing CIT, HLA mismatch, DGF, and acute rejection, recipient race (black), younger age, and nondiabetics status; and donor race (black) and older age for elevated SCr and long-term graft failure. CONCLUSION: Donor (age), race (black), recipient race (black), immunologic variables (HLA mismatch, DGF, acute rejection) were identified as important risk factors for elevated SCr at 1 year post-transplantation and long-term graft failure. Elevated SCr should be used as a short-term marker for predicting long-term transplant survival.     

Transplantation Outcomes in Primary Hyperoxaluria

Optimal transplantation strategies are uncertain in primary hyperoxaluria (PH) due to potential for recurrent oxalosis. Outcomes of different transplantation approaches were compared using life‐table methods to determine kidney graft survival among 203 patients in the International Primary Hyperoxaluria Registry. From 1976–2009, 84 kidney alone (K) and combined kidney and liver (K + L) transplants were performed in 58 patients. Among 58 first kidney transplants (32 K, 26 K + L), 1‐, 3‐ and 5‐year kidney graft survival was 82%, 68% and 49%. Renal graft loss occurred in 26 first transplants due to oxalosis in ten, chronic allograft nephropathy in six, rejection in five and other causes in five. Delay in PH diagnosis until after transplant favored early graft loss (p = 0.07). K + L had better kidney graft outcomes than K with death‐censored graft survival 95% versus 56% at 3 years (p = 0.011). Among 29 year 2000–09 first transplants (24 K + L), 84% were functioning at 3 years compared to 55% of earlier transplants (p = 0.05). At 6.8 years after transplantation, 46 of 58 patients are living (43 with functioning grafts). Outcomes of transplantation in PH have improved over time, with recent K + L transplantation highly successful. Recurrent oxalosis accounted for a minority of kidney graft losses.     

Post-transplant renal function in the first year predicts long-term kidney transplant survival

BACKGROUND: Improvements in long-term kidney graft survival have been recently noted. However, the reasons for this were unclear. This study examined post-transplant renal function within the first year as an independent variable influencing long-term survival. METHODS: The influence of demographic characteristics (age, sex, race); transplant variables (cadaver versus living donor, cold ischemia time, HLA mismatching, delayed graft function and transplant year), and post-transplant variables (immunosuppressive agents for the prevention of acute rejection, clinical acute rejection and post-transplant renal function in the first year) on graft survival were analyzed for 105,742 adult renal transplants between 1988 and 1998. Renal function in the first year was expressed as serum creatinine at six months and one year and delta creatinine (change in serum creatinine between 6 months and 1 year). Graft half-life was used to measure long-term survival. RESULTS: During this 11-year period, the one-year serum creatinine values for cadaver recipients steadily improved, from 1.82 +/- 0.82 mg/dL in 1988 to 1.67 +/- 0.82 mg/dL in 1998 (P < 0.001), as did the graft half-life. There was a progressive decline in graft half-life for each incremental increase of six month, one year and Delta creatinine for living and cadaver donor transplants as well for cadaver transplants with donor age > and < or =50 years. The Relative Hazard (RH) for graft failure was 1.63 (1.61, 1.65; P < 0.0001) with each increment of 1.0 mg/dL of serum creatinine at one year post-transplant and it increased to 2.26 (2.2, 2.31; P < 0.0001) when the Delta creatinine was 0.5 mg/dL. The RH reduction for graft failure was substantially lower for the years 1993, 1996, 1997 and 1998 when post-transplant renal function was not included in the model (P < 0.05). However, the RH reduction per year was not different when post-transplant creatinine was included in the model, 1.01 (0.94 to 1.05; P = 0.89). CONCLUSION: In conclusion, one-year creatinine and Delta creatinine values predict long-term renal graft survival. Recent improvements in graft half-life are related to conservation of renal function within the first year post-transplantation.     

Long-term survival after liver transplantation in 4,000 consecutive patients at a single center

OBJECTIVE: To evaluate the long-term survival outcomes of a large cohort of liver transplant recipients and to identify static and changing factors that influenced these outcomes over time. SUMMARY BACKGROUND DATA: Liver transplantation has been accepted as a therapeutic option for patients with end-stage liver disease since 1983, with continual improvements in patient survival as a result of advances in immunosuppression and medical management, technical achievements, and improvements in procurement and preservation. Although many reports, including registry data, have delineated short-term factors that influence survival, few reports have examined factors that affect long-term survival after liver transplantation. METHODS: Four thousand consecutive patients who underwent liver transplantation between February 1981 and April 1998 were included in this analysis and were followed up to March 2000. The effect of donor and recipient age at the time of transplantation, recipient gender, diagnosis, and year of transplantation were compared. Rates of retransplantation, causes of retransplantation, and cause of death were also examined. RESULTS: The overall patient survival for the entire cohort was 59%; the actuarial 18-year survival was 48%. Patient survival was significantly better in children, in female recipients, and in patients who received transplants after 1990. The rates of retransplantation for acute or chronic rejection were significantly lower with tacrolimus-based immunosuppression. The risk of graft failure and death was relatively stable after the first year, with recurrence of disease, malignancies, and age-related complications being the major factors for loss. CONCLUSION: Significantly improved patient and graft survival has been observed over time, and graft loss from acute or chronic rejection has emerged as a rarity. Age-related and disease-related causes of graft loss represent the greatest threat to long-term survival.     

单个移植中心连续4000例肝移植后长期生存情况回顾

目的：评价大样本肝移植病人长期生存情况和分析影响移植疗效的动静因素。背景回顾：自1983年以来肝移植被接受为治疗终末期肝病的主要选择之一，随着免疫抑制剂的发展，手术技术的不断完善，取肝及保存方法改进，生存期获不断延长。虽然报告影响近期生存因素的文章甚众，但分析影响长期生存因素者却不多见。方法：回顾性分析1981年2月至1998年4月连续施行的4000例肝移植资料（随访至2000年3月），并对移植时供，受体年龄，受体性别和诊断以及上份等因素进行比较；也统计了再移植率，再移植原因和死亡原因。结果：全组的总生存率为59％，统计18年生存率为48％；小儿，女性和1990年以后接受移植的病人生存情况产好。以FK506为基础的免疫抑制剂使因急，慢性排斥反应而施行的再移植率显著下降，手术一年后，移植肝脏丧失功能病人死亡的曲线相对趋于平稳，疾病复发，急性肿瘤和与年龄相关的并发症是移植物丧失功能的最主要因素。结论：随着年供的推移，病人和移植物的生存活情况获显著改善，由急性，慢性排斥反应所致的移植物失功已属十分罕见，与年龄相关和疾病相关的移植物失功，已构成肝移植患者长期生存的最大威胁。     

Effect of donor age on the outcome of living-related kidney transplantation

The study compared the results of kidney transplantation from living-related donors older and younger than 60 years. The 273 kidney graft recipients were divided into group 1 (115 recipients of older grafts) and group 2 (158 recipients of younger grafts). The frequency of acute rejection (AR) episodes was similar in both groups but slow graft function occurred more frequently in group 1. The frequency of chronic renal allograft dysfunction in the first post-transplant year was significantly higher in group 1 than in group 2. Patient and graft survival was significantly worse in group 1. Risk factors for graft loss were the difference between donor and recipient age and AR. Donor age and graft function were risk factors for patient death. Although kidneys from older donors provide a statistically poorer transplant outcome, they are clinically acceptable, especially when waiting time is prolonged and access to dialysis limited.     

A 100% 2-year graft survival can be attained in high-risk 15-kg or smaller infant recipients of kidney allografts

BACKGROUND: Infants make up the most high-risk, difficult to care for subgroup undergoing kidney transplantation, with the lowest 1- and 2-year graft survival rates of any other age group. The principal causes of graft loss have been graft thrombosis, primary nonfunction, technical error, and irreversible acute rejection. HYPOTHESIS: Infants undergoing kidney transplantation can achieve near 100% graft survival at 2 years following surgery, despite their very high-risk status. DESIGN: Analysis of 45 consecutive kidney transplants performed in patients weighing less than or equal to 15 kg during an 8-year period beginning August 1991. Patients included complex referrals from throughout the United States and all received transplants and were cared for by the same pediatric kidney transplantation team. RESULTS: Mean weight at transplantation was 11. 2 kg. Renal failure was due to congenital or urologic causes in the majority (53%) of cases. Size-discrepant adult-sized kidney grafts were transplanted in 80% of patients; 64% received live-donor grafts; 78% were receiving dialysis prior to transplantation; and 27% had extremely small bladders (<20 cm(3)) requiring modification of the ureteral implantation. Excluding 1 transplant-unrelated death, graft and patient survival at 2 years was 100%. Eight-year patient and graft survival rates (for our combined live and cadaver donor series) were 89.6% and 84.6%, respectively. This compares favorably with much lower graft survival in low-risk adult recipients. Delayed graft function occurred in only 1 patient (2%). Rate of incidence of rejection was 9.3% within 2 years of transplantation and the overall rejection rate was 15.5%. No graft was lost to vascular thrombosis, primary nonfunction, technical error, or acute rejection. The mean creatinine level was 53.04 micromol/L (0.6 mg/dL) and 61.9 micromol/L (0.7 mg/dL) at 1 and 2 years, respectively, and 88.4 micromol/L (1.0 mg/dL) at 3, 4, and 5 years after transplantation. CONCLUSION: One hundred percent 2-year and excellent 8-year graft survival rates can be achieved in what has historically been the highest-risk and most difficult to care for patient subgroup undergoing kidney transplantation.     

Impact of Acute Rejection Episodes on Long-Term Graft Survival Following Simultaneous Kidney-Pancreas Transplantation

Although it is well established that acute rejection is one of the major risk factors for chronic graft loss following kidney transplantation, its effect on long-term graft survival following simultaneous kidney-pancreas transplants (SKPTs) is less well known. We analyzed a large cohort of SKPTs and cadaver kidney transplants reported to the United Network for Organ Sharing database during 1988-97, to determine the impact of acute rejection episodes on long-term kidney and pancreas graft survival. Only patients whose kidney and pancreas grafts had survived for at least 1 year were included. Other potential risk factors influencing long-term graft survival were included in the analysis. Of the 4251 SKPTs, 45% had no acute rejection, 36% had kidney only rejection, 3% had pancreas only rejection, and 16% had both kidney and pancreas rejection within the 1st year post transplant. The 5-year kidney and pancreas graft survival rates adjusted for other risk factors were 91% and 85%, respectively; for those with no acute rejection episodes, 88% and 84%, respectively; for those with kidney only rejection, 94% and 83%, respectively; for those with pancreas only rejection; and 86% and 78%, respectively, for those with both kidney and pancreas rejection. The relative risk (RR) of kidney graft failure was 1.32 when acute rejection involved the kidney graft only, while the RR was 1.53 when the rejection involved both organs. We conclude that acute rejection episodes have a negative impact on the long-term kidney graft survival in the SKPT population similar to that in the cadaver kidney transplant population. Patients who had acute rejection episodes of both kidney and pancreas have the worst long-term graft survival.     

The changing causes of graft loss and death after kidney transplantation

BACKGROUND: The results of kidney transplantation have improved markedly over the last three decades. Despite this, patients still lose grafts and die. We sought to determine whether the causes of graft loss and death have changed over the last 30 years. METHODS: We reviewed patients who underwent transplantation or who died between January 1, 1970 and December 31, 1999. We compared the causes of graft loss or death for three decades: 1970 to 1979, 1980 to 1989, and 1990 to 1999. RESULTS: From January 1, 1970 to December 31, 1999, we performed 2501 kidney transplantations in 2225 patients. For the three periods, 210, 588, and 383 patients lost their grafts, respectively. Graft survival increased substantially. Graft loss occurred later after transplantation, with 36.0% losing grafts in the first year during 1970 to 1970, 22.8% during 1980 to 1989, and 11.4% during 1990 to 1999. Death with a functioning graft increased from 23.8% for 1970 to 1979 to 37.5% for 1990 to 1999. Concomitantly, rejection as a cause of graft loss fell from 65.7% for 1970 to 1979 to 44.6% for 1990 to 1999. Approximately two thirds of the patients who died after transplantation died with a functioning graft and one third died after returning to dialysis. Cardiac disease as a cause of death increased from 9.6% for 1970 to 1979 to 30.3% for 1990 to 1999. Deaths from cancer and stroke also increased significantly over the three decades from 1.2% and 2.4%, respectively, for 1970 to 1979, to 13.2% and 8.0%, respectively, for 1990 to 1999. CONCLUSIONS: The causes of graft loss and death have changed over the last three decades. By better addressing the main causes of death, cardiac disease, and stroke with better prevention, graft loss due to death with a functioning graft will be reduced.     

Clinical factors which influence the long-term survival of kidney allografts donated from haploidentical donors

All patients with renal transplants are very much concerned about their chance of long-term graft function. Chronic rejection is the most common cause of decline in function and graft failure, and after the first post-transplant year, 3–4% of recipients lose their graft every year [4]. However, the cause, time of onset and mechanism of decline in graft function are not clear. Also unclear is whether clinical and laboratory parameters may predict patients who are at risk of developing chronic rejection. The aim of this study was to find the marker which may determine long-term graft survival in the azathioprine era and in the cyclosporine era.     

Immunologic factors: the major risk for decreased long-term renal allograft survival

BACKGROUND: Both antigen-dependent (immunologic) and non-antigen-dependent (nonimmunologic) factors have been implicated in long-term renal allograft loss. Differentiating between these two factors is important because prevention strategies differ. METHODS: To isolate the importance of these 2 factors, we studied long-term actuarial graft survival in a cohort of adult kidney recipients who underwent transplants at a single institution between January 1, 1984 and October 31, 1998. Excluded were recipients with graft loss as a result of death with function, technical failure, primary nonfunction, and recurrent disease, leaving 1587 recipients (757 cadaver [CAD], 830 living donor [LD]) who would be at risk for graft loss secondary to both immunologic and nonimmunologic factors. These recipients were analyzed in the following 2 groups: those treated for a previous episode of acute rejection (AR) (Group1; n = 588; 328 CAD, 260 LD) and those with no AR (Group 2: n = 999; 429 CAD, 570 LD). Actuarial graft survival and causes of graft loss were determined for each group. Presumably, graft loss in Group 1 would be caused by immunologic and nonimmunologic factors; graft loss in Group 2 would be caused primarily by nonimmunologic factors. RESULTS: The 10-year graft survival rate (censored for death with function, technical failure, primary nonfunction, and recurrent disease) in Group 2 was 91%. In contrast, the 10-year graft survival rate in Group 1 was 45% (P<0.001 vs. Group 2). Causes of graft loss in Group 2 were chronic rejection in 1.8% (3.0% CAD, 0.9% LD), de novo disease, 0.4%; sepsis, 0.2%; discontinuation of immunosuppressive therapy, 0.3%; and unknown, 0.6%. In contrast, 23.8% (29.9% CAD, 16.2% LD) of recipients in Group 1 had graft loss caused by chronic rejection (P = 0.001 vs. Group 2). CONCLUSIONS: This very low incidence of chronic rejection in recipients without previous AR suggests that immunologic factors are the main determinants of long-term kidney transplant outcome; nonimmunologic factors in isolation may have only a minimal impact on long-term graft survival.     

Simultaneous pancreas-kidney transplantation: is the failure of the grafts also simultaneous?

INTRODUCTION: It is well known that after a simultaneous pancreas and kidney transplantation (SPKT) there is a higher incidence of pancreatic graft loss in the acute period, due to technical problems. However, there is little information about the survival of pancreatic and kidney grafts 1 year after transplantation. AIMS: To analyze the causes of long-term graft loss of SPKT in our hospital and to determine if this loss occurs simultaneously or is isolated. PATIENTS AND METHODS: We analyzed the data of 63 SPKTs performed between February 1983 and October 2005, including the cases with normal renal and pancreatic function after 1 year of transplantation, and with a loss of one or two organs during the follow-up period (8 +/- 4 years). We defined simultaneous SPKT failure as failure that occurs at the same time or when the period between pancreatic and renal graft failure is shorter than 9 months. RESULTS: In 28 patients (44%), there was a simultaneous graft failure, whereas in 35 (56%) the loss of function occurred in only one organ or in both, but separately. Death was responsible for 75% (21/28) of simultaneous graft losses, representing 25% (9/35) of isolated graft failures. Cardiovascular disease was the leading cause of death. In 14 of 35 isolated graft failures, there was loss of renal and pancreatic function (11/14 kidney failed first) with a 2.9 +/- 2.3 years of interval. In 12 cases there was only loss of pancreatic function, whereas in nine cases the affected organ was the kidney. Graft chronic nephropathy and chronic rejection in the pancreas were the main causes of graft failure. CONCLUSIONS: The main cause of simultaneous SPKT failure is patient death; however, among isolated or separated SPKT failures, the kidney failed first, more frequently.     

Kidney Transplantation Outcomes in Canadian Aboriginals

Aboriginal populations experience a very high rate of end-stage renal disease (ESRD); however, little is known about the outcomes of transplantation in this population. We performed a retrospective database review to determine the short- and long-term outcomes of kidney transplantation in Aboriginals. Adult Aboriginal (AB) and Caucasian (C) individuals receiving primary kidney transplants between 1969 and 2003 in Manitoba, Canada were examined. A total of 705 recipients were included (126 AB and 579 C). AB recipients were younger, had different etiologies of ESRD, longer cold-ischemic times for deceased donor transplants, and higher peak panel reactive antibody levels. At 1 year post-transplant, there was no difference in serum creatinine, acute rejection or graft survival between AB and C recipients. However, AB recipients experienced greater weight gains early post-transplant and were more likely to develop post-transplant diabetes mellitus. AB recipients exhibited inferior 10-year graft (AB 26% vs. C 47%, p < 0.01) and patient survival (AB 50% vs. 75%, p < 0.01). When graft survival was censored for death with a functioning graft, there was no difference between the two groups. Multivariate analysis revealed AB race to be an independent predictor of premature graft failure and patient death. In conclusion, kidney transplant outcomes have historically been inferior in the Manitoba population of Canadian Aboriginals.